We have developed a novel technology to amplify distantly related gene sequences based on consensus-degenerate hybrid oligonucleotide primers (CODEHOPs). Unlike the "Basic Local Sequence Alignment Tool (BLAST) used to detect related sequences in silico, CODEHOPs can search for related sequences in the genome content of all living organisms, and is not limited to the relatively few sequences contained within the existing electronic databases. CODEHOPs are designed from highly conserved regions of multiply aligned protein sequences from members of a protein family and are used in PCR amplification to rapidly and specifically identify distantly related orthologs and paralogs belonging to a common gene family. We have developed software to predict CODEHOPs and made it freely accessible on the WWW. Since its inception, the CODEHOP technology has proven invaluable for the identification of unknown viral pathogens as well as the identification and structural characterization of viral and cellular genes implicated in various biological processes and disease. CODEHOPs and the related software are currently being used successfully worldwide by an increasing number of scientists working on widely different model organisms and subjects. However, the need to improve and broaden the scope of our technology has become apparent from the many e-mails we have received from CODEHOP users. To address these issues is critical to achieve our long-term goal to uniquely provide the scientific community with a user-friendly, fast and reliable technology for the identification and structural comparison of related genes within a broad range of organisms. The objective of this application is to further develop the unique CODEHOP technology and validate improvements and changes by identifying and characterizing novel cellular genes and viral pathogens that are implicated in cancer pathogenesis. Our AIMS are to further develop and improve the CODEHOP software and CODEHOP-based PCR technology and add all outcomes to the existing CODEHOP web site. The significance of the proposed project lies in increasing the user-friendliness, speed and accuracy of this important technology. We expect that this will lead to an increased pace of discovery of pathogens implicated in disease, as well as genes of biological and biomedical importance.